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作 者:Jinbin Hao Yin Guo Hui Zhou Haomiao Ouyang Jinghua Yang Wenxia Fang Cheng Jin
机构地区:[1]State Key Laboratory of Mycology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [2]University of Chinese Academy of Sciences,Beijing,China [3]Colleg of Life Science and Technology,Guangxi University,Nanning,China [4]Institute of Biological Sciences and Technology,Guangxi Academy of Sciences,Nanning,China
出 处:《mLife》2024年第4期537-550,共14页微生物(英文)
基 金:supported by the National Key Research and Development Program of China(2021YFC2300400);the National Natural Science Foundation of China(32371337).
摘 要:Glycosylphosphatidylinositol(GPI)anchoring is one of the conserved posttranslational modifications in eukaryotes that attach proteins to the plasma membrane.In fungi,in addition to plasma membrane GPI‐anchored proteins(GPI‐APs),some GPI‐APs are specifically released from the cell membrane,secreted into the cell wall,and covalently linked to cell wall glucans as GPI‐anchored cell wall proteins(GPI‐CWPs).However,it remains unclear how fungal cells specifically release GPI‐CWPs from their membranes.In this study,phospholipase PlcH was identified and confirmed as a phospholipase C that hydrolyzes phosphate ester bonds to release GPI‐APs from the membrane of the opportunistic fungal pathogen Aspergillus fumigatus.Deletion of the plcH gene led to abnormal conidiation,polar abnormality,and increased sensitivity to antifungal drugs.In an immunocompromised mouse model,theΔplcH mutant showed an attenuated inflammatory response and increased macrophage killing compared with the wild type.Biochemical and proteomic analyses revealed that PlcH was involved in the localization of various cell wall GPI‐APs and contributed to the cell wall integrity.Our results demonstrate that PlcH can specifically recognize and release GPI‐CWPs from the cell membrane,which represents a newly discovered secretory pathway of GPI‐CWPs in A.fumigatus.
关 键 词:Aspergillus fumigatus cell wall protein GPI‐anchored protein immune response macrophage killing
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